Chronic kidney disease (CKD) is common and is associated with substantial morbidity and mortality, which is largely due to an increased incidence of cardiovascular diseases. Calcitriol (1,25-dihydroxyvitamin D3, the active vitamin D hormone) is a particularly promising treatment to reduce cardiovascular morbidity and mortality in CKD. The kidneys are the major site of calcitriol production, and circulating calcitriol concentrations fall dramatically in CKD, even when standard vitamin D supplements are administered. Provocative cardioprotective actions of calcitriol have been demonstrated in animal-experimental models, and observational studies of people with CKD consistently demonstrate associations of calcitriol use with reduced mortality. However, no clinical trial has tested the effects of calcitriol on clinical outcomes. The objective of the proposed research is to determine, in a randomized clinical trial, whether calcitriol use (0.25 mcg by mouth daily) reduces the risk of cardiovascular disease events among people with CKD (estimated glomerular filtration rate 20-59 mL/min/1.73m2). During the UH2 phase of our study, we aim to demonstrate the feasibility of integrating a well-designed pragmatic clinical trial of calcitriol ito the clinical care infrastructure of Group Health Cooperative, a large integrated health care system. During the UH3 phase of our study, the study aim is to test the effect of calcitriol plus usual care, compared with usual care alone, on the occurrence of clinically relevant cardiovascular outcomes (primary composite outcome of myocardial infarction, acute coronary syndrome, stroke, hospitalized heart failure, or cardiovascular death) among 4,370 Group Health patients with CKD. Secondary outcomes will include components of the primary composite outcome and progression of CKD to end stage renal disease. We have assembled a multidisciplinary team of collaborators from Group Health and the University of Washington to develop and conduct this pragmatic clinical trial. The study will maximize efficiency, economy, and external validity by applying minimal eligibility criteria and by utilizing an extensive array f electronic resources to identify participants, deliver and monitor the study intervention, and ascertain study outcomes. Individual-level randomization, standardized protocols to promote retention and adherence, and rigorous ascertainment of study outcomes will enhance internal validity.